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Slide 2 Slide 3 Slide 4 Research student example of development and test of computer-based instrument 1) Schematics of comparison polarimeter 2) Build and test of instrument for change in phase () between the standard and sample polarimeter cells Sorey Research Group (continued) Delta Phi () Concentration (g/10mL) -0.02110.00 0.1170.50 0.2851.00 0.3671.50 0.5552.00 3) Calibration and validation with D-Fructose 0.00g/10mL D-Fructose 2.00g/100mL D-Fructose Timothy L. Sorey, PhD. Central Washington University soreyt@cwu.edu Slide 5 Why Natural Products? Track record of success Discovery process High-demand skills Field work component Rationale for Selection of Organisms of Interest Ecological: suspected chemical defenses or communication Geographic: extreme or difficult to access environments Taxonomic: infrequently or never before studied Ethnographic: traditional or folklore uses We have been heavily focused on the chemistry of the plant genus Dalea, after investigating many different genera using the above rationale. Current projects: Dalea formosa Status:manuscript ready for submission. 7 new and 1 known compound(s). Activity: antifungal and related. Collaborator: Marcin Kolaczkowski (Poland). Dalea searlsiae Status: Isolation and characterization nearly complete. 3 new and 5 known compounds. Activity: Antibacterial and antiinsectan. Collaborators: Eric Foss (CWU, Biology) and Patrick Dowd (USDA-ARS, Peoria, IL). Dalea ornata Status: Early stages of purification of extracts. Activity: Anti-hookworm and antibacterial. Collaborators: Blaise Dondji and Eric Foss (CWU, Biology). Psorothamnus emoryi (Dalea emoryi) Status: Early stages of purification. No associated activity to date Belofsky Research Slide 6 Thomas Research Group: Effects of Environmental Factors on Mitochondrial Function and Reactive Oxygen Species Generation 4 e - 1 e- O 2 H2O2H2O2 OH Fe 2+ Cellular respiration and ATP synthesis Reactive Oxygen Species (ROS) Antioxidant and Repair processes Cell Signaling Apoptosis: Cell Death Slide 7 Mitochondrial Energetics & ROS Slide 8 Aerobic organisms have engineered antioxidant defenses against ROS Superoxide Dismutase (MnSOD) 2O 2.- + 2H + H 2 O 2 + O 2 Glutathione Peroxidase (GPx) GSH = intracellular thiol H 2 O 2 + 2 GSH 2 H 2 O + GSSG Glutathione Reductase NADPH, H + + GSSG 2 GSH + NADP + Nicotinamide Nucleotide Transhydrogenase NADH, H + NAD + + NADPH, H + facilitates GSH recycling and removal of H 2 O 2 Slide 9 Methods and results Examples of new flavanoids found Structure determination of unknown compounds Extensive 1D and 2D NMR spectroscopy Recent upgrade of our own 400 MHz instrument to run advanced 2D experiments like HSQC & HMBC High resolution mass spectrometry Sent to the University of Iowa We continue to find new, interesting and active compounds from this plant genus! Slide 10 Kroll Lab: Graded Expression of Transcription Factors Regulates Neocortical Arealization Altering the concentration gradients of any of these transcription factors results in predictable changes in the size of neocortical areas: normal Emx2 reduced Emx2 change in gradient change in area sizes The big question now are: 1) How are these boundaries established 2) How do these transcription factors transmit positional information within the cells but, there are always clear boundaries separating the areas We are attempting to answer these questions by finding the proteins to which these transcription factors interact. Slide 11 Fabry Research Group Design and Synthesis of Novel Enzyme Inhibitors My research group is interested in addressing biologically and medically important questions. The focal point of our research is the design and synthesis of small molecule inhibitor scaffolds against therapeutically important enzymes. Our goal is to find orally active inhibitors that could become lead compounds for further drug discovery. During this process, we are developing new and improving already known synthetic chemistry methodologies. To achieve our goals we use all the modern tools of medicinal chemistry and organic synthesis. Organic Synthesis Medicinal Chemistry Pharmacology Dr. Levente Fabry-Asztalos; fabryl@cwu.edu; (509) 963-2887; SCI 302F Computer Modeling Slide 12 Fabry Research Group Design and Synthesis of Novel Enzyme Inhibitors Also, as a joint research effort with a computer science group we develop and extensively test new molecular modeling and computational chemistry techniques. This endeavor centers on molecular modeling, as well as computational intelligence techniques, which include neural networks, fuzzy systems, evolutionary computation, and biology inspired computational models. Dr. Levente Fabry-Asztalos; fabryl@cwu.edu; (509) 963-2887; SCI 302F Computer Modeling Pharmacology Medicinal Chemistry Organic synthesis Slide 13 Rivera Research Group Investigation of macromolecular complexes and their interactions with guest molecules. Polyelectrolyte/surfactant Complex (PSC) H2OH2O TiO 2 (s) Goals: To understand how the PSC interacts with guest molecules. Understand the effects of the structure of the guest molecule on the its interaction with the PSC. Understand the influence of different surfactants on the formation of the PSC. Slide 14 Analytical Techniques Used: ATR-FTIR, UV-vis, quartz crystal microbalance, and surface tension measurement. Original Data Matrix - Matrix of Dye Spectra = Matrix with Dye removed - = Since macromolecular systems are inherently complex multivariate data analysis techniques such need to be applied to the acquired data in order to fully understand the systems. Example of a constraint applied to the UV-vis data set. Slide 15 Diaz Research Group electron migration and trapping in luminescent materials Dr. Diazs research involves the study of electron- hole (e-h) pair transport and trapping in doped luminescent materials under vacuum ultraviolet (VUV) excitation. Excitation by VUV radiation leads to the formation of an e-h pair in the host. In order for luminescence to occur this e-h pair must be trapped by the rare earth dopant. However, the electron may also be trapped by bulk killers (impurities or defects), or it may be lost to surface states. In this figure YBO 3 is the host and Eu 3+ is the dopant. The purpose of our research is to quantify the fate of the e-h pair after absorption of a VUV photon takes place. Above is another view of the process, which shows the electronic states involved. Once created, the e-h pair migrates through the lattice until it is trapped by killers or by a dopant. Dopant states are in blue, and loss to killers is indicated by the dashed line. The overall efficiency of host excitation once a photon is absorbed is given by host = t * qe, where t is the transfer efficiency and qe is the quantum efficiency of the dopant after the e-h pair is trapped. The transfer efficiency is then host / qe. These quantities are determined spectroscopically via absorbance and excitation measurements essentially comparing the amount of light the material absorbs to the amount of light emitted by the dopant after absorption. Slide 16 Once transfer efficiency data are collected they are modeled using the equation on the left. The transfer efficiency is simply the ratio of the rate of transfer to dopants (also called activators) divided by the combined rate of trapping by killers and activators. The multiplier S loss is equal to 1 when no energy is lost to the surface, and approaches zero as more surface loss takes place. If transfer efficiency data are collected for a series of dopant concentrations, the ratio and the value of S loss can be determined. Theoretical curves are shown below on the left, while recent data on nanocrystalline YBO 3 :Eu 3+ are shown on the right. With particle sizes > 500 nm no surface loss is observed, while at 25 nm more than 40% of absorbed energy is lost to the surface. Diaz Research Group electron migration and trapping in luminescent materials Slide 17 Chemistry with Computers Yingbin Ge 17 Astrochemistry in Ice Europa Ganymede Callisto Si nanoclusters emit bright light C 3 H 8 + 1/2O 2 C 3 H 6 + H 2 O Bulk silicon Pt n From water to water oxide to hydrogen peroxide Slide 18 My recent presentations and research interests are posted on http://www.cwu.edu/~yingbin/research.html My CV including a publication list is posted on http://www.cwu.edu/~yingbin/cv/cv.pdf My questions to you are which one of my papers or projects interests you the most and why? Slide 19 2.Pollution Monitoring at Mt. Rainier and North Cascades National Parks (NPS) Precipitation High elevation lakes 1.Iron in Aerosol Particles (NSF) Implications on Global Climate and Human Health Crustal/Marine Anthropogenic Johansen Research - Current Projects 3.Chemistry of Faulty Wines Analyses Method development (Continuing Ed. And Biology) Slide 20 Nature of the Work - Examples Laboratory Field Solar Simulator Study photochemistry in synthesized and ambient aerosols. Aerosol Collector Collect particles in 4 size fractions at sea and regionally. QUANTITATIVE ANALYSIS Instruments in Chemistry, Geology, EMSL IC, Chemiluminescence FIA, ICPMS, XPS Slide 21 Chamberland Research Group: Synthetic/Medicinal Organic Chemistry We Make New Molecules That Target Biological Systems We Aim to be First! Current Research Projects Total synthesis of clavatadine A, a potent Factor XIa inhibitor (antithrombotic agent) Total synthesis of -carboline analogues, active against fungi, bacteria, and leukemia Total synthesis of phidianidines A and B, active anti-cancer agents Future Research Goals Design, synthesize, and perform biological testing of clavatadine A and -carboline analogues to develop new, more effective medicines for thrombosis and cancer Synthesize new natural products that are biologically active and structurally interesting Computational chemistry research: the alpha effect vs. the anomeric effectwho wins? Dr. Stephen Chamberland chambers@cwu.edu; (509) 963-1126; SCI 302H Slide 22 Chamberland Research Group: Synthetic/Medicinal Organic Chemistry Clavatadine A project: First total synthesis of a new FXIa inhibitor inhibits Result: hemostasis vs. excess clotting and/or hemorrhage Carbamate formation between an azidoisocyanate and a dibrominated phenol as the key step Clavatadine A binds to the FXIa active site, then is cleaved by the enzyme